PROJECT SUMMARY / DESCRIPTION Does maternal infection by the SARS-CoV-2 virus during pregnancy harm the developing fetal brain or increase the sensitivity to later developmental and environmental insults? he novel coronavirus (Covid-19) outbreak has fundamentally altered the child health landscape, ushering in sweeping changes in the social and economic fabric within which children grow. The rapidity of these environment changes, coupled with the relatively novelty of the SARS-CoV-2 virus and the widespread nature of infections, have presented multiple pressing questions. Among the unknowns that directly affect newborn and child health are: 1. How does Covid-19 infection during pregnancy effect the developing fetus or subsequent infant neurodevelopment? And 2. How will the unprecedented scale and scope of concurrent environmental changes impact child health and neurodevelopment? Unfortunately, over the course of the outbreak, the impact on children has been slow to be recognized with studies of Covid-19 infection or effects in infants and young children sparse to nonexistent. Moreover, while the health and economic impacts of the Covid-19 outbreak have been felt by everyone, the most severe effects have be felt by racial and ethnic minorities and lower income families. Thus, the most sensitive families and children already at risk for worsened neurodevelopmental outcomes are disproportionately and more intensely affected. Studies of newborns and infants are, therefore, critical to designing effective guidelines of care for expectant mothers, optimizing early care and support for mothers and their newborns, and prioritizing pre- and postnatal interventions. This supplement proposal aims to contribute important and timely evidence for these outcomes by characterizing neurodevelopmental profiles in infants born to mothers with and without antenatal Covid-19 infection, and examining the concurrent impact of social, economic, and substance use factors. Building on two existing and on-going studies of infant neurodevelopment (R34DA050284 and UH3OD023313), with deeply characterised longitudinal neuroimaging, neurocognitive, socioeconomic, demographic, psychosocial and biospecimen data, we will first investigate differences in brain structure, function, and connectivity development from birth to 1yr of age in infants born to mothers who were infected by the SARS-CoV-2 virus during pregnancy and born between May 1, and Sept. 1, 2020, compared to infants recruited at the same time but to non-infected mothers. We will also examine the impact of infection timing during pregnancy and symptom severity on brain measures. Next, we will compare these brain development trends to data from children who turned 1year old prior to Jan. 1, 2020, allowing us to examine the impact of specific environmental factors, including maternal and infant stress, nutrition, sleep health, and parent- child interaction that have changed due to outbreak-related lock-down and social distancing polices. We will further look at these environmental factors through a racial and socioeconomic lens, examining differences across race and income dimensions.